Abstract
Mutations in a gene encoding a multitransmembrane protein, termed presenilin 1 (PS1), are causative in the majority of early-onset cases of AD. To determine the topology of PS1, we utilized two strategies: first, we tested whether putative transmembranes are sufficient to export a protease-sensitive substrate across a lipid bilayer; and second, we examined the binding of antibodies to specific PS1 epitopes in cultured cells selectively permeabilized with the pore-forming toxin, streptolysin-O. We document that the "loop," N-terminal, and C-terminal domains of PS1 are oriented toward the cytoplasm.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amyloid beta-Protein Precursor / chemistry
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Amyloid beta-Protein Precursor / genetics
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Animals
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CHO Cells / chemistry
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CHO Cells / physiology
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COS Cells / chemistry
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COS Cells / physiology
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Cricetinae
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Cytoplasm / chemistry
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Exons / genetics
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Humans
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Membrane Proteins / chemistry*
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Membrane Proteins / genetics
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Mutation / physiology
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Presenilin-1
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Protein Conformation
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Protein Structure, Tertiary
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / genetics
Substances
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Amyloid beta-Protein Precursor
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Membrane Proteins
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PSEN1 protein, human
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Presenilin-1
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Recombinant Fusion Proteins